Expandable elements for delivery of electric fields

ABSTRACT

A method, system, and device for electroporation. A system may include a medical device with a plurality of electrodes borne on an expandable element and an energy generator in communication with the electrodes. The energy generator may have processing circuitry configured to selectively deliver electroporation energy to at least one of the electrodes. The processing circuitry may determine whether an alert condition is present and, if so, cease the delivery of electroporation energy to one or more electrodes identified as the cause of the alert condition and/or prevent the delivery of electroporation energy to the one or more electrodes identified as the cause of the alert condition. The energy generator may also be configured to deliver electroporation energy in a sequence of a plurality of energy delivery patterns to enhance lesion formation.

CROSS-REFERENCE TO RELATED APPLICATION

This application is a divisional of U.S. application Ser. No. 15/663301,filed Jul. 28, 2017, titled EXPANDABLE ELEMENTS FOR DELIVERY OF ELECTRICFIELDS.

TECHNICAL FIELD

The present invention relates to methods, systems, and devices forenhancing the efficiency and efficacy of ablation energy delivery andtissue mapping. In particular, the present invention relates to improvedelectrodes, electrode configurations, and energy delivery patterns ofablation energy.

BACKGROUND

Many individuals suffer from various cardiac issues which requiretreatments and interventions, including ablation. As people age, cardiacrhythm irregularity becomes an increasingly bigger problem and cansometimes result in death. One type of cardiac rhythm irregularity isatrial fibrillation, which is an irregular and often rapid heart ratethat can increase the risk of stroke, heart failure, and otherheart-related complications in an individual. In atrial fibrillation,the two upper chambers of the heart may beat chaotically and/orirregularly and lack coordination with the two lower chambers of theheart. The heart can beat irregularly and quiver instead of beatingefficiently and effectively to move blood into the ventricles. Anindividual with atrial fibrillation may experience shortness of breath,weakness, and heart palpitations. Sometimes an individual with atrialfibrillation requires treatment which may include using ablation tocorrect this abnormality.

Ventricular tachycardia is another type of cardiac rhythm irregularitywhere there is a fast heart rhythm which begins with the ventricles.This condition may be caused by a malfunction in the heart's electricalsystem. When the heart's electrical impulses are disrupted and theelectrical signals are sent too quickly, ventricular tachycardia canresult and this rapid heartbeat may not give the ventricles enough timeto fill with blood before the heart contracts. As a result, the heartmay not be able to pump enough blood to the rest of the body. Somesymptoms of ventricular tachycardia include lightheadedness, dizziness,and fainting. Ablation may be used to treat and/or manage ventriculartachycardia.

Medical procedures such as cardiac ablation using one or more energymodalities are frequently used to treat such conditions. However,complications may arise when using these procedures. For example, energydelivery may cause collateral damage to non-targeted tissue. Further,the procedure may not cause adequate lesion formation and, therefore,the underlying condition still persists. Certain energy modalities, suchas electroporation, are delivered in short bursts that are less likelyto cause thermal damage to non-target tissue. However, it may still bechallenging to create adequate lesions, such as fully circumferential,contiguous, and/or transmural lesions, and fewer than all cells in atreated area may be irreversibly electroporated.

SUMMARY

The present invention advantageously provides a methods, systems, anddevices for enhancing the efficiency and efficacy of ablation energydelivery to tissue. In one embodiment, a medical system includes amedical device configured to electroporate tissue, the medical deviceincluding an expandable element, the expandable element having aplurality of electrodes; and an energy generator in communication withthe plurality of electrodes, the energy generator having processingcircuitry configured to: deliver electroporation energy to the pluralityof electrodes; receive data from the plurality of electrodes; determinewhether an alert condition is present based on the data received fromthe plurality of electrodes; and at least one of cease a delivery ofelectroporation energy to the plurality of electrodes and prevent thedelivery of electroporation energy to the plurality of electrodes whenthe processing circuitry determines the alert condition is present.

In one aspect of the embodiment, the data includes impedancemeasurements.

In one aspect of the embodiment, the plurality of electrodes isconfigured to be uniformly spaced when the expandable element isexpanded.

In one aspect of the embodiment, each of the plurality of electrodes isconfigured to record at least one impedance measurement, the processingcircuitry being configured to receive the at least one impedancemeasurement from each of the plurality of electrodes and selectivelyactivate at least one of the plurality of electrodes based on the atleast one impedance measurement received from each of the plurality ofelectrodes.

In one aspect of the embodiment, the system further includes a mappingsystem and the energy generator and processing circuitry are furtherconfigured to selectively connect each of the plurality of electrodes tothe mapping system and record intracardiac electrogram signals from eachof the plurality of electrodes.

In one aspect of the embodiment, the expandable element has a distalportion and a proximal portion, the plurality of electrodes beingdisposed on the distal portion of the expandable element.

In one aspect of the embodiment, the medical device may further includeat least one electrode distal to the expandable element.

In one aspect of the embodiment, the at least one electrode distal tothe expandable element is on a secondary medical device that ispositionable distal to the medical device.

In one aspect of the embodiment, the medical device further includes adistal tip that extends distally beyond the expandable element, the atleast one electrode distal to the expandable element being on the distaltip.

In one aspect of the embodiment, the energy generator is configured todeliver electroporation energy to the plurality of electrodes in asequence of a plurality of energy delivery patterns.

In one aspect of the embodiment, the processing circuitry is configuredto automatically switch between the plurality of energy deliverypatterns such that a pulse train of electroporation energy is deliveredin each of the plurality of energy delivery patterns at least once whenthe system is in use.

In one aspect of the embodiment, the medical device further includes alongitudinal axis, each of the plurality of electrodes having a teardropshape that is tapered in a proximal-to-distal direction, the pluralityof electrodes being radially arranged around the longitudinal axis.

In one embodiment, a medical system includes a medical device configuredto electroporate an area of tissue, the medical device including: aballoon having a distal portion and a proximal portion; and a pluralityof electrodes disposed on the distal portion of the balloon, each of theplurality of electrodes being configured to record impedance signalsfrom the area of tissue and deliver electroporation energy to the areaof tissue; and an energy generator in communication with the pluralityof electrodes, the energy generator having processing circuitryconfigured to: receive impedance signals from the plurality ofelectrodes; identify at least one electrode of the plurality ofelectrodes that is in contact with the area of tissue based on impedancesignals received from the plurality of electrodes; determine whether theplurality of electrodes has uniform spacing when the balloon is inflatedbased on impedance signals received from the plurality of electrodes;allow a delivery of electroporation energy to the plurality ofelectrodes when the processing circuitry determines the plurality ofelectrodes has uniform spacing when the balloon is inflated; andselectively deliver electroporation energy to the at least one electrodeof the plurality of electrodes that the processing circuitry identifiesas being in contact with the area of tissue.

In one aspect of the embodiment, the medical device further includes alongitudinal axis, each of the plurality of electrodes having a teardropshape that is tapered in a proximal-to-distal direction, the pluralityof electrodes being radially arranged around the longitudinal axis.

In one aspect of the embodiment, the medical balloon has acircumference, each of the plurality of electrodes having a circularshape and the plurality of electrodes being radially arranged around thecircumference of the balloon.

In one aspect of the embodiment, the energy generator is configured todeliver electroporation energy to the plurality of electrodes in aplurality of energy delivery patterns.

In one aspect of the embodiment, the energy generator is configured todeliver bipolar electroporation energy between adjacent pairs of theplurality of electrodes to the area of tissue, the plurality of energydelivery patterns being a sequence of at least five energy deliverypatterns.

In one aspect of the embodiment, the energy generator is configured todeliver monopolar electroporation energy between at least one of theplurality of electrodes and a supplemental electrode located distal tothe balloon.

In one embodiment, a method for electroporating tissue includespositioning an expandable element of a medical device proximate an areaof target tissue, the expandable element including a plurality ofelectrodes, each of the plurality of electrodes being configured torecord impedance measurements; recording impedance measurements witheach of the plurality of electrodes; transmitting the recorded impedancemeasurement to an energy generator; identifying, based on the recordedimpedance measurements, at least one electrode of the plurality ofelectrodes that is in contact with the area of target tissue and that isa predetermined distance from at least one adjacent electrode of theplurality of electrodes; and then delivering electroporation energy tothe identified at least one electrode in a sequence of energy deliverypatterns by selectively one of activating and deactivating each of theat least one electrode of the plurality of electrodes.

In one aspect of the embodiment, the method further includes deliveringthe sequence of energy delivery patterns such that there is a delayfollowing each energy delivery pattern in the sequence of energydelivery patterns and each energy delivery pattern in the sequence ofenergy delivery patterns has a duration that is at least as long as acorresponding following delay.

In one embodiment, a medical system may include: a medical deviceconfigured to electroporate a targeted area of tissue, the medicaldevice including: an expandable element having a plurality of splines,each of the plurality of splines having a distal portion and a proximalportion, the plurality of splines being transitionable between a linearfirst configuration and an expanded second configuration; and aplurality of electrodes disposed on the distal portions of the pluralityof splines, each of the plurality of electrodes being configured torecord impedance signals from the targeted area of tissue and deliverelectroporation energy to the targeted area of tissue; and an energygenerator in communication with the plurality of electrodes, the energygenerator having processing circuitry configured to: deliverelectroporation energy to the plurality of electrodes in a sequence of aplurality of energy delivery patterns; and automatically switch betweenthe plurality of energy delivery patterns of the sequence of theplurality of energy delivery patterns such that a pulse train ofelectroporation energy is delivered in each of the plurality of energydelivery patterns at least once when the system is in use.

In one aspect of the embodiment, the processing circuitry is furtherconfigured to: receive impedance signals from the plurality ofelectrodes; identify at least one electrode of the plurality ofelectrodes that is located proximate the targeted area of tissue basedon the impedance signals received from the plurality of electrodes; andselectively deliver electroporation energy to the at least one electrodeof the plurality of electrodes that the processing circuitry identifiesas being located proximate the targeted area of tissue.

In one aspect of the embodiment, the processing circuitry is furtherconfigured to: determine whether the plurality of electrodes has uniformspacing when the plurality of splines are in the expanded secondconfiguration based on impedance signals received from the plurality ofelectrodes; and allow a delivery of electroporation energy to theplurality of electrodes when the processing circuitry determines theplurality of electrodes has uniform spacing when the plurality ofsplines are in the expanded second configuration.

BRIEF DESCRIPTION OF THE DRAWINGS

A more complete understanding of the present invention, and theattendant advantages and features thereof, will be more readilyunderstood by reference to the following detailed description whenconsidered in conjunction with the accompanying drawings wherein:

FIG. 1 shows an exemplary system including a first embodiment of amedical device for electroporating tissue;

FIG. 2 shows an exemplary system including a second embodiment of amedical device for electroporating tissue;

FIG. 3 shows an exemplary system including a third embodiment of amedical device for electroporating tissue;

FIG. 4 shows a fourth embodiment of a medical device for electroporatingtissue;

FIG. 5 shows a side view of a distal portion of a medical device havinga first configuration of electrodes, the electrodes being activated in afirst energy delivery pattern;

FIG. 6 shows a front view of the distal portion of the medical deviceshown in FIG. 3, the electrodes being activated in the first energydelivery pattern;

FIG. 7 shows a side view of a distal portion of a medical device havingthe first configuration of electrodes, the electrodes being activated ina second energy delivery pattern;

FIG. 8 shows a front view of the distal portion of the medical deviceshown in FIG. 5, the electrodes being activated in the second energydelivery pattern;

FIG. 9 shows a side view of a distal portion of a medical device havingthe first configuration of electrodes, the electrodes being activated ina third energy delivery pattern;

FIG. 10 shows a front view of the distal portion of the medical deviceshown in FIG. 7, the electrodes being activated in the third energydelivery pattern;

FIG. 11 shows a side view of a distal portion of a medical device havinga second configuration of electrodes, the electrodes being activated ina first energy delivery pattern;

FIG. 12 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a second energy delivery pattern;

FIG. 13 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a third energy delivery pattern;

FIG. 14 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a fourth energy delivery pattern;

FIG. 15 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a fifth energy delivery pattern;

FIG. 16 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a sixth energy delivery pattern;

FIG. 17 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a seventh energy delivery pattern;

FIG. 18 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin an eighth energy delivery pattern;

FIG. 19 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a ninth energy delivery pattern;

FIG. 20 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin a tenth energy delivery pattern; and

FIG. 21 shows a side view of a distal portion of a medical device havingthe second configuration of electrodes, the electrodes being activatedin an eleventh energy delivery pattern.

DETAILED DESCRIPTION

The devices, systems, and methods disclosed herein provide for increasedefficacy and efficiency of treatment procedures by enhancing lesionformation and depth, and also allow for the acquisition of enhancedmapping signals. Specifically, described herein are device and systemconfigurations and energy delivery patterns that facilitate theirreversible electroporation of target tissue cells by deliveringelectrical field energy to the target tissue in a number of vectors. Thedevices and systems described herein enhance patient safety and increaseablation efficiency by allowing for the selective delivery of energy toindividual electrodes based on electrode-tissue contact/proximity and/orproximity between electrodes.

Before describing in detail exemplary embodiments that are in accordancewith the disclosure, it is noted that components have been representedwhere appropriate by conventional symbols in drawings, showing onlythose specific details that are pertinent to understanding theembodiments of the disclosure so as not to obscure the disclosure withdetails that will be readily apparent to those of ordinary skill in theart having the benefit of the description herein. For simplicity,electric fields are not shown in order to simply depict the relativepolarities of monophasic or biphasic pulsed voltages or currents.

As used herein, relational terms, such as “first,” “second,” “top” and“bottom,” and the like, may be used solely to distinguish one entity orelement from another entity or element without necessarily requiring orimplying any physical or logical relationship or order between suchentities or elements. The terminology used herein is for the purpose ofdescribing particular embodiments only and is not intended to belimiting of the concepts described herein. As used herein, the singularforms “a”, “an” and “the” are intended to include the plural forms aswell, unless the context clearly indicates otherwise. It will be furtherunderstood that the terms “comprises,” “comprising,” “includes” and/or“including” when used herein, specify the presence of stated features,integers, steps, operations, elements, and/or components, but do notpreclude the presence or addition of one or more other features,integers, steps, operations, elements, components, and/or groupsthereof.

Unless otherwise defined, all terms (including technical and scientificterms) used herein have the same meaning as commonly understood by oneof ordinary skill in the art to which this disclosure belongs. It willbe further understood that terms used herein should be interpreted ashaving a meaning that is consistent with their meaning in the context ofthis specification and the relevant art and will not be interpreted inan idealized or overly formal sense unless expressly so defined herein.

In embodiments described herein, the joining term, “in communicationwith” and the like, may be used to indicate electrical or datacommunication, which may be accomplished by physical contact, induction,electromagnetic radiation, radio signaling, infrared signaling oroptical signaling, for example. The terms “active” or “powered” may beused to indicate electrodes that are connected to either the positive ornegative polarity of the electrical energy source/energy generator,thereby producing an electric current between such powered but oppositepolarity electrodes. In a similar manner, electrodes termed as“neutral,” “inactive,” “disconnected,” “deactivated”, “decoupled,” or“unpowered” are those electrodes that are not connected to either of thepolarities of the source of electrical energy/energy generator duringsuch energy deliveries. In a similar manner, during energy deliveriesfrom active electrodes, the active electrodes may be disconnected fromthe mapping system during the period of energy delivery and reconnectedto the mapping system upon cessation of energy delivery. Additionally,following a set of deliveries of energy between active electrode pairs,the roles of active and neutral electrodes may be reversed such that theactive pairs become neutral and the formerly neutral electrodes becomethe active electrodes, thus substantially altering the electric fieldvectoring between the first and second sets of energy deliveries. Onehaving ordinary skill in the art will appreciate that multiplecomponents may interoperate and modifications and variations arepossible of achieving the electrical and data communication.

Referring now to the drawing figures in which like referencedesignations refer to like elements, a first exemplary embodiment of amedical system constructed in accordance with the principles of thepresent invention is shown in FIG. 1, generally designated as “10.” Thesystem 10 may generally include a medical device 12, such as a catheter,that may be coupled directly to an energy supply, such as anelectroporation energy generator 14 including an energy control,delivering, and monitoring system, or indirectly through a deviceelectrode distribution system 16 (which may also be referred to hereinas a catheter electrode distribution system or CEDS). Further, themedical device 12 may include one or more diagnostic or treatmentregions for the energetic, therapeutic, and/or investigatory interactionbetween the medical device 12 and a treatment site. As a non-limitingexample, the treatment region(s) may include a plurality of electrodes18 configured to deliver electroporation energy to a tissue area inproximity to the electrodes 18. Although the system is discussed hereinas being used for electroporation, it will be understood that themedical device 12, generator 14, and/or other system components mayadditionally or alternatively be configured for use with a variety ofenergy modalities, including pulsed field ablation, radiofrequency (RF)ablation, laser ablation, microwave ablation, cryoablation, and thelike.

The medical device 12 may serve both as a treatment device and a mappingdevice. The medical device 12 may include an elongate body 22 passablethrough a patient's vasculature and/or proximate to a tissue region fordiagnosis and/or treatment. For example, the medical device 12 may be acatheter that is deliverable to the tissue region via a sheath orintravascular introducer (not shown). The elongate body 22 may define aproximal portion 24, a distal portion 26, and a longitudinal axis 28,and may further include one or more lumens disposed within the elongatebody 22 thereby providing mechanical, electrical, and/or fluidcommunication between the elongate body proximal portion 24 and theelongate distal portion 26.

The medical device 12 may further include one or more expandableelements 30 at, coupled or affixed to, or otherwise on the elongate bodydistal portion 26 for energetic, therapeutic, diagnostic and/orinvestigatory interaction between the medical device 12 and a treatmentsite or region. As a non-limiting example, the device 12 may include anexpandable element 30, such as a balloon as shown in FIGS. 1-3 and 521.The medical device 12 may also include a plurality of electrodes 18 onthe expandable element 30. The electrodes 18 on the expandable element30 are not shown in FIGS. 1-3 for simplicity, but are shown anddescribed in more detail in FIGS. 5-21. The electrodes 18 may becomposed of any suitable electrically conductive material(s), such asmetal or metal alloys. In a non-limiting example, the plurality ofelectrodes 18 may be deposited or printed onto an outer surface of theexpandable element 30, or may be integrated with the material of theexpandable element 30. Additionally or alternatively, the plurality ofelectrodes 18 may be adhered to, mounted to, affixed to, or otherwisedisposed on an inner surface of the expandable element 30 or on theouter surface of the expandable element 30. In one embodiment, themedical device 12 may include a first expandable element 30A locatedwithin a second expandable element 30B (for example, as shown in FIG.1). In this configuration, one or more electrodes 18 optionally may belocated within an interstitial space between the first 30A and second30B expandable elements.

As is discussed in more detail below, the expandable element 30 may havea proximal portion 32 and a distal portion 34 (for example, as shown inFIG. 5). In one embodiment, the plurality of electrodes 18 are locatedon the distal portion 34 of the expandable element 30. However, it willbe understood that the plurality of electrodes 18 may be additionally oralternatively located at other locations on the medical device 12, suchas on the proximal portion 32 of the expandable element 30. The locationof a delineation between the proximal portion 32 and the distal portion34 of the expandable element 30 may depend on the size, shape, andconfiguration of the expandable element 30. In general, however, thedistal portion 34 of the expandable element 30 may include at least thearea of the expandable element that is configured to be in contact withan area of tissue that is oriented orthogonal to, or at leastsubstantially orthogonal to, the elongate body longitudinal axis 28 whenthe medical device 12 is in use. However, at least some of the pluralityof electrodes 18, or at least a portion of some of the plurality ofelectrodes 18, may also be located on a portion of the expandableelement 30 that is not in contact with tissue when the medical device 12is in use. Further, the expandable element 30 may be in fluidcommunication with a source of inflation fluid and/or cryogenic fluid(not shown) for ablation of tissue by cryoablation.

The medical device 12 may further include a handle 36 coupled to theelongate body proximal portion 24. The handle 36 may include circuitryfor identification and/or use in controlling of the medical device 12 oranother component of the system. Additionally, the handle 36 may alsoinclude connectors that are mateable to the generator 14 and/or the CEDS16 to establish communication between the medical device 12 and thegenerator 14. The handle 36 may also include one or more actuation orcontrol features that allow a user to control, deflect, steer, orotherwise manipulate a distal portion of the medical device 12 from theproximal portion of the medical device 12.

The system 10 may further include one or more supplemental electrodes18′ located distal to the expandable element 30. In one embodiment, theone or more supplemental electrodes 18′ are coupled to, affixed to,printed on, or otherwise disposed on a secondary medical device 38 thatis positionable at a location distal to the expandable element 30 andelectrodes 18. For example, as shown in FIG. 2, the medical device 12may include a lumen 40, such as a guidewire lumen, that is slidablylocated within the elongate body 22 and extends through the expandableelement 30. The secondary medical device 38 may be a guidewire includingone or more supplemental electrodes 18′ and may be sized and configuredsuch that at least a portion of the secondary medical device 38 may bereceived within the lumen 40. Further, the secondary medical device 38may be longitudinally movable within the lumen 40 such that at least aportion of the secondary medical device 38, such as a distal portionbearing the supplemental electrode(s) 18′, may be extended out of adistal opening of the lumen 40 to position the supplemental electrode(s)18′ distal to the expandable element 30. In some modes of operation, thesupplemental electrode(s) 18′ of the secondary medical device 38 may beconnected to the same polarity of the generator 14, thereby causing thesupplemental electrode(s) 18′ to operate as a single electrode, whichmay facilitate the creation of linear lesions between the supplementalelectrode(s) 18′ and the electrode(s) 18. In other modes of operation,only the secondary medical device 38 may be used to deliverelectroporation energy, with some supplemental electrode(s) 18′selectively connected to a first (for example, positive) polarity of thegenerator 14 and other supplemental electrode(s) 18′ selectivelyconnected to a second (for example, negative) polarity of the generator14 to deliver a variety of energy delivery patterns. The secondarymedical device 38 may also be used to anchor and/or help navigate themedical device 12 and/or to map tissue.

Additionally or alternatively, the medical device 12 may include adistal tip 39 that extends distally from the distal portion 34 of theexpandable element 30. The distal tip 39 may include one or moresupplemental electrodes 18′ (for example, as shown in FIG. 3). Inanother embodiment, the one or more supplemental electrodes 18′ may belocated on a secondary device that is separate from the medical device12 and positionable at a location that is proximate the position of themedical device 12 (not shown). For example, the medical device 12 may belocated within the left atrium proximate a pulmonary vein, whereas thesecondary device is located in the pericardial space proximate themedical device 12. In another embodiment, the medical device 12 mayinclude a distal electrode 18″ on the distalmost portion of theexpandable element 30 (for example, as shown in FIGS. 5-10). Allelectrodes of the system (including electrodes 18 on the medical device12 and any supplemental electrodes 18′) may be in electricalcommunication with the generator 14. Thus, energy may be deliveredbetween one or more of the electrodes 18 on the expandable element andone or more supplemental electrodes 18′ to create different ablationpatterns, such as ablation patterns that are linear or extended in aproximal-to-distal direction instead of or in addition tocircumferential ablation patterns.

In one embodiment as shown in FIG. 4, the expandable element 30 mayinclude one or more splines or thin flexible membranes 41. The spline(s)41 may be used without a balloon or inflatable element, or maysurrounding or be located within a balloon or inflatable element (notshown). One or more electrodes 18 may be adhered to, mounted to, affixedto, or otherwise disposed or coupled to the spline(s) 41. This may allowfor smaller electrode size and enhancement of mapping signal recording.In one embodiment, the medical device 12 may include eight splines 41(five splines of which are shown in FIG. 4), each spline 41 having adistal portion 41A and a proximal portion 41B. The distal portion 41A ofeach spline 41 may include a plurality of electrodes 18. The proximalportion 41B of each spline 41, and the portions of the distal portion41A of each spline 41 located between electrodes 18, optionally may beinsulated (for example, may include an insulative coating). Further, thedistal portion 41A of each spline 41, such as a distal tip of eachspline, may be adhered to, affixed to, or otherwise coupled to a distalportion of a lumen 40 (for example, an guidewire lumen as shown in FIG.2), though which a secondary medical device 38 may be passed, asdiscussed above. Longitudinal movement of the lumen 40 within theelongate body 22 may change the size, shape, and configuration of thespline(s) 41. For example, advancement of the lumen 40 within theelongate body 22 may extend the spline(s) 41 and reduce the diameter ofthe expandable element 30, whereas retraction of the lumen 40 within theelongate body 22 may retract the spline(s) 41 and increase the diameterof the expandable element 30. That is, the spline(s) 41 may betransitionable between a linear, or at least substantially linear, firstconfiguration and an expanded second configuration in which each spline41 is curvilinear, bowed, or arcuate (for example, as shown in FIG. 4).

The energy generator 14 may be within or in electrical communicationwith a control unit 42 that may further include or be in electricalcommunication with one or more other system components, such as one ormore displays 44, user input devices 46, secondary medical devices 38, amapping and/or navigation system 48 (which may also be referred toherein as a recording system 48), the CEDS 16, and the like. Forsimplicity, all system components other than the medical device 12 andthe secondary medical device 38 (if included in the system 10) may becollectively referred to as being part of the control unit 42. Inaddition to being configured to deliver ablation energy, such aselectroporation energy, the plurality of electrodes 18 may also beconfigured to perform diagnostic functions, such as to collectintracardiac electrograms (EGM) and/or monophasic action potentials(MAPs) as well as performing selective pacing of intracardiac sites fordiagnostic purposes. Recorded signals may be transferred from the deviceelectrode energy distribution system 16 to the control unit 42.Alternatively, in some embodiments, the recorded signals may betransferred directly from the medical device 12 to the control unit 42(for example, to the energy generator 14).

The plurality of electrodes 18 may also be configured to recordimpedance measurements from tissue and/or fluids surrounding and/or incontact with the electrodes 18 in order to monitor the proximity totarget tissues and quality of contact with, for example, an area oftarget tissues CEDS 16. The plurality of electrodes 18 may also beconfigured to record impedance measurements from tissue before, during,and/or after the delivery of electroporation energy to determine orqualify lesion formation in the target tissue. The generally accepteddefinition of the term impedance is used herein: a complex ratio ofsinusoidal voltage to current in an electric circuit or component,except that as used herein, impedance shall apply to any region or spacethrough which some electrical field is applied and current flows. Thegenerator 14 may be configured to receive impedance measurements fromthe plurality of electrodes 18 and use the impedance measurement to atleast one of activate an electrode from the plurality of electrodes 18or deactivate an electrode from the plurality of electrodes 18.Electrodes 18 may be activated based upon the impedance measurementsduring ablation. When targeted tissue is identified with the impedancemeasurement, energy can be delivered to those electrodes in closeproximity or in contact with specified tissue and electrodes 18 whichare in contact with blood or tissue that is not desirable may bedeactivated based upon a specific impedance measurement. The CEDS 16 mayinclude high speed relays to disconnect/reconnected specific electrodes18 of the plurality of electrodes 18 from/to the generator 14 during anenergy delivery procedure. In a non-limiting example, the relays mayautomatically disconnect/reconnect electrodes 18 to enable the medicaldevice 12 to record mapping signals between deliveries ofelectroporation energy pulses.

Although not shown, the system 10 may include one or more sensors tomonitor the operating parameters throughout the system, in addition tomonitoring, recording or otherwise conveying measurements or conditionswithin the medical device 12 or the ambient environment at the distalportion of the medical device 12. For example, each electrode 18 mayinclude a temperature sensor, pressure sensor, or other sensor. Thesensor(s) may be in communication with the generator 14 and/or the CEDS16 for, for example, initiating or triggering one or more alerts and/ortherapeutic delivery modifications during operation of the medicaldevice 12.

Electroporation is a phenomenon causing cell membranes to become “leaky”(that is, permeable for molecules for which the cell membrane mayotherwise be impermeable or semipermeable). Electroporation, which mayalso be referred to as electropermeabilization, pulsed electric fieldtreatment, non-thermal irreversible electroporation, irreversibleelectroporation, high frequency irreversible electroporation, nanosecondelectroporation, or nanoelectroporation, involves the application ofhigh-amplitude pulses to cause physiological modification (i.e.,permeabilization) of the cells of the tissue to which the energy isapplied. These pulses preferably may be short (for example, nanosecond,microsecond, or millisecond pulse width) in order to allow theapplication of high voltage, high current (for example, 20 or more amps)without long duration(s) of electrical current flow that may causesignificant tissue heating and muscle stimulation. The pulsed electricenergy may induce the formation of microscopic defects that result inhyperpermeabilization of the cell membrane. Depending on thecharacteristics of the electrical pulses, an electroporated cell cansurvive electroporation, referred to as “reversible electroporation,” ordie, referred to as “irreversible electroporation” (IEP). Reversibleelectroporation may be used to transfer agents, including geneticmaterial and other large or small molecules including but not limited totherapeutic agents, into targeted cells for various purposes, includingthe alteration of the action potentials of cardiac myocytes.

As such, the control unit 42 may include processing circuitry 50 thatincludes software modules containing instructions or algorithms toprovide for the automated and/or semi-automated operation andperformance of various system 10 functions. For example, the processingcircuitry 50 may include a processor and a memory in communication withthe processor, and the memory may include instructions that, whenexecuted by the processor, configure the processor to perform sequences,calculations, or procedures described herein and/or required for a givenmedical procedure. In one embodiment, the processing circuitry 50 is acomponent of the generator 14 within the control unit 42. The processingcircuitry 50 may be further configured to deliver electroporation energyor another type of energy to the electrodes 18 and determine whether analert condition is present. The alert condition may be based at least inpart on signals received from the electrode(s) 18 (for example,impedance measurements recorded by the electrode(s) 18) and/or one ormore other system sensors. In one embodiment, the generator 14 may beconfigured to cease the delivery of electroporation energy to one ormore electrodes 18 and/or prevent the delivery of electroporation energyto one or more electrodes 18 when the processing circuitry determinesthe alert condition is present.

The system 10 may further include a plurality of surface electrodes 52in communication with the generator 14 directly or indirectly throughthe CEDS 16. The plurality of surface electrodes 52 may be part of apositioning and navigation system that allows for the localization ofthe electrodes within three-dimensional space within the patient's bodythrough the transmission and receipt of positioning and navigationsignals to and from the generator 14. When the surface electrodes 52 areapplied to the skin of a patient, they may be used, for example, tomonitor the patient's cardiac activity to determine pulse train deliverytiming at the desired portion of the cardiac cycle (that is, to recordand transmit electrical activity measurements to the generator 14 and/orfor navigation and location of the device 12 within the patient). Thesurface electrodes 52 may be in communication with the generator 14 fordetermining the timing during a cardiac cycle at which to initiate ortrigger one or more alerts or therapeutic deliveries during operation ofthe medical device 12. In addition to monitoring, recording, orotherwise conveying measurements or conditions within the medical device12 or the ambient environment at the distal portion 26 of the medicaldevice 12 (for example, electrocardiogram or ECG signals and/ormonophasic action potentials or MAPs), the surface electrodes 52 may beused to record measurements such as temperature, electrode-tissueinterface impedance, delivered charge, current, power, voltage, work, orthe like. An additional neutral electrode patient ground patch (notshown) may be used to evaluate the desired bipolar electrical pathimpedance, as well as monitor and alert the operator upon detection ofundesired and/or unsafe conditions. As used herein, the term “bipolarablation” or “bipolar energy” may refer to the delivery of electricpulses between two electrodes (for example, between two electrodes 18 ofthe medical device 12), rather than between a single device electrodeand a ground electrode (for example, as is the case in unipolarablation). The generator 14 may be configured to deliver a samplingpulse prior to delivery of a full series or “pulse train” of pulsedelectric field ablative therapy pulses. Such a preliminary samplingpulse may provide measurements of relative electrical impedance betweenelectrodes and warning of inappropriate electrode configurations such asoverlapping electrodes and/or electrodes that are positioned too closelytogether and that could result in, for example, a short circuitcondition. The medical device 12 may be configured to deactivate certainelectrodes 18 if they are overlapping and/or positioned too closelytogether. Additionally, such preliminary pulses may be used to evaluatesuch conditions as relative proximity of individual electrodes 18 toensure an appropriate voltage is to be applied to the electrodes duringsubsequent energy delivery and the voltage that is delivered to theelectrodes 18 may be adjusted. These preliminary pulses may also beapplied to assess whether the electrodes are positioned properlyrelative to the target tissue allowing the electrodes 18 to berepositioned in relation to the target tissue. The preliminary pulsesmay be delivered with or without automated, immediate, subsequentdelivery of one or more therapeutic pulse trains.

When the medical device 12 is initially positioned before initiation ofa delivery of electroporation energy, one or more checks may beperformed to determine whether the expandable element 30 and/orelectrodes 18 are optimally positioned to ablate an area of targettissue without causing unintended damage to non-target tissue and/ordamage to the medical device 12 or generator 14. The check(s) may failif the processing circuitry 50 determines one or more alert conditionsare present. In one non-limiting example, the medical device 12 may benavigated to a target treatment site to perform an electroporationprocedure, such as electroporation of cardiac tissue, renal tissue,airway tissue, and/or organs or tissue within the cardiac space.Specifically, the expandable element 30 may be expanded or collapsed (insome embodiments, inflated or deflated) and may adjust to the shape of aparticular tissue region. When the expandable element 30 is expanded orinflated, the electrodes may initially deliver a sampling pulse tomeasure, as a non-limiting example, relative electrical impedance.Depending upon the impedance measurement, a warning may be provided (forexample, an audible warning and/or a visual warning, such as a LED lightor text or symbolic indication shown on one or more displays 44) toalert that certain electrodes 18 may not be properly positioned, whichthe processing circuitry 50 may identify as an alert condition. Forexample, certain electrodes 18 may be in contact with or proximatetissue that is not intended to be ablated or certain electrodes 18 maybe too close to one another for the safe delivery of energy. Anyelectrodes 18 that have an impedance measurement that triggers thewarning may be deactivated so that energy will not be delivered to thoseparticular electrodes 18. The medical device 12 may be repositioned andanother sampling pulse may measure relative electrical impedance todetermine if a warning is generated for any of the electrodes 18 whenthe medical device is 12 in the new position. In one embodiment,impedance measurements may be recorded by each electrode 18 at each oftwo frequencies (for example, 12 kHz and 100 kHz) and those impedancemeasurements for each electrode 18 may be compared to each other, toimpedance measurement(s) from other electrode(s) 18, and/or to impedancemeasurements recorded by supplemental electrode(s) 18′, surfaceelectrodes 52, and/or other system electrodes. If no warning is providedon the display 44, the electrodes 18 may be activated by the processingcircuitry 50, thus being capable of transmitting energy from thegenerator 14. Additionally or alternatively, if a warning is generatedfor one or more electrodes 18, the processing circuitry 50 maydeactivate or prevent the delivery of electroporation energy to thoseelectrodes 18 without requiring the medical device 12 to berepositioned.

As a further non-limiting example, the system 10 may perform a check todetermine whether the expandable element 30 has been properly expandedor inflated and, therefore, to determine whether there is adequatespacing between adjacent electrodes 18 for the safe and/or effectivedelivery of electroporation energy. When the expandable element 30 isexpanded or inflated prior to the delivery of electroporation energy,portions of the expandable element 30 may not expand as intended and/ormay adhere together, which may cause adjacent electrodes 18 to belocated very close to each other. If electroporation energy weredelivered in a bipolar fashion between electrodes without adequatespacing or that were in contact with each other, a spike in thedelivered current may occur. Put another way, when there is uniformspacing between electrodes 18, the electric field between the electrodes18 will have a uniform intensity. Additionally, delivering energy fromelectrodes 18 on an improperly expanded or inflated expandable element30 (for example, an expandable element with impaired/compromisedsymmetry) may result in the formation of non-contiguous ornon-transmural lesions. The processing circuitry 50 may identify suchimproper inflation as an alert condition. After the expandable element30 is expanded (such as by inflation), a sampling pulse may be deliveredto determine if the expandable element 30 has fully expanded/inflated.If there are portions of the expandable element 30 are adheringtogether, the impedance signal will be altered and the processingcircuitry 50 may alert the user. The electrodes 18 that are associatedwith the altered impedance signal may be deactivated and/or theexpandable element 30 may then be at least partially deflated/collapsedand then reinflated/re-expanded to full expansion. Alternatively, themedical device 12 may be removed from the patient and replaced with anew device. These checks may enable the processing circuitry 50 todetermine which electrode(s) 18 should be activated or deactivated, aninflation status of the expandable element (for example, whether theexpandable element has symmetrically expanded/inflated and/or whetherthe electrodes 18 are properly spaced from each other), whether toinitiate the delivery of electroporation energy, and/or otherparameters. In a similar manner, if the medical device 12 includes anexpandable element 30 with splines 41, the electrodes 18 located on thesplines 41 may be found to be in close proximity after expansion of thesplines 41. In such a situation, the sampling pulse and impedance checkswould provide a warning and/or alert the user to re-expand the splines41 to achieve the desired uniform electrode spacing.

Once the checks have been performed and the processing circuitry 50determines the delivery of electroporation energy should be initiatedand, optionally, to which electrode(s) 18, transmission ofelectroporation energy from the generator 14 to the electrode(s) 18 maybe commenced. The generator 14 may be configured and programmed todeliver pulsed, high-voltage electric fields appropriate for achievingreversible or irreversible electroporation. In one embodiment, thegenerator 14 may be configured to deliver irreversible electroporationenergy that is sufficient to induce cell death for purposes ofcompletely blocking an aberrant conductive pathway along or throughcardiac tissue, destroying the ability of the cardiac tissue topropagate or conduct cardiac depolarization waveforms and associatedelectrical signals.

One or more electrodes 18 may record impedance measurements before,during, and/or after the delivery of electroporation energy. In oneembodiment, the electrode(s) 18 that are activated and that transmitenergy may be used to record impedance measurements from the area oftissue to which the energy is delivered. Additionally or alternatively,the electrode(s) 18 that are deactivated and do not transmit energy maybe used to record impedance measurements from nearby tissue and/orsurrounding fluid. The processing circuitry 50 may use the recordedimpedance measurements to determine if the tissue to which energy hasbeen delivered (that is, the treated tissue) has been adequatelyablated. The electrode(s) 18 may continue delivering energy, or may bereactivated to deliver energy, to area(s) of tissue from which impedancemeasurements have been recorded that indicate sufficient ablation hasnot occurred.

Referring now to FIGS. 5-21, the electrodes 18 and energy deliverypatterns are disclosed in more detail. In general, energy may bedelivered during a medical procedure, such as an ablation procedure, inone or more of the energy delivery patterns discussed herein. Theseenergy delivery patterns, and other energy delivery patterns notexpressly disclosed herein, may be achieved by selectively deactivatingone or more electrodes 18 (such as by disconnecting those electrodes 18from both the positive and negative polarities of the generator 14)and/or activating one or more electrodes 18 (such as by connecting eachof those electrodes to either the positive or negative polarity of thegenerator 14) disconnecting one or more electrodes 18 from the generator14. Optionally, the electrodes 18 may be configured such that differentportions of the electrode 18 may be selectively activated ordeactivated. Further, the electrodes 18 may be closely spaced to eachother (for example, may have spacing of between approximately 1 mm andapproximately 3 mm) and may be relatively small (for example, betweenapproximately 1.5 mm and approximately 3 mm in length), which mayenhance mapping signal recording. These same electrodes 18 may also beselectively connected to/disconnected from the generator 14 to deliverelectroporation energy (for example, high voltage pulses or pulse trainshaving a short duration).

In one general embodiment, all electrodes 18 may be connected to themapping system 48 to record one or more mapping measurements, such asECG signals. In this embodiment, one or more adjacent electrodes 18 maybe connected to the mapping system 48 to reduce spacing betweenelectrodes 18 activated for mapping and, therefore, to enhance signalfidelity. After the mapping measurements have been recorded, one or moreelectrodes 18 may be disconnected from the mapping system 48 andconnected to one of the polarities of the generator 14 for the deliveryof electroporation energy. When delivering electroporation energy, theelectrodes 18 may be connected to the generator 14 such that electrodesimmediately adjacent to each other are not both activated at the sametime. This configuration may allow the generator 14 to apply relativelyhigh voltages to electrodes 18 that are separated by adequate distanceto produce a desired uniform electric field strength distribution.Alternatively, the electrodes 18 may be connected to the generator 14such that adjacent electrodes are both activated. Alternatively, agroups of first electrodes 18 may be connected to the same polarity ofthe generator 14 and all other electrodes 18 (that is, a larger secondgroup of electrodes 18) may be connected to the opposite polarity of thegenerator 14, which may enhance the electric field strength under thesmaller first group of electrodes 18. In this way, customized energydelivery patterns may be used to create specific lesion sizes, shapes,and depths.

A number of energy delivery patterns may be used during a single medicalprocedure. This may cause the treated tissue to experience multipleelectric field vector directions, thereby causing a larger percentage ofexposed cells to become irreversibly electroporated. The processingcircuitry 50 may be programmed and configured to automatically orsemi-automatically switch electrode connections (for example, throughthe CEDS 16) multiple times during a medical procedure to deliver two ormore energy delivery patterns sequentially. In one non-limiting example,the processing circuitry 50 may receive a signal by the user to initiatethe procedure (which may include electroporation and/or mapping signalrecording). When the procedure is initiated, the processing circuitry 50may be configured to cause the generator 14 to deliver a train ofelectrical pulses where the electrical field vectoring is betweenclosely spaced electrodes 18, and then immediately thereafter cause thegenerator 14 to deliver a train of electrical pulses where theelectrical field vectoring is between more widely spaced electrodes 18.Each pulse train for each delivery pattern may have a duration ofbetween approximately 10 milliseconds (ms) and approximately 100 ms.These patterns may be repeated and/or further be immediately followed byone or more other patterns, with no delay, or period in which noelectroporation energy is delivered, between energy delivery patterns,or with a minimal delay (for example, approximately 10 ms) betweenenergy delivery patterns that is not longer than the duration of thepreceding pulse train. As a non-limiting example, the processingcircuitry 50 may be configured to automatically deliver a sequence oftwo or more energy delivery patterns in rapid succession by selectivelyactivating or deactivating each of the plurality of electrodes. In oneembodiment, the processing circuitry 50 may be configured toautomatically and sequentially deliver a sequence of at least fiveenergy delivery patterns by selectively activating or deactivating eachof the plurality of electrodes. In one embodiment, the processingcircuitry 50 may be configured to automatically and sequentially delivera sequence of eleven energy delivery patterns by selectively activatingor deactivating each of the plurality of electrodes (for example, thoseenergy delivery patterns shown in FIGS. 11-21). Further, the processingcircuitry 50 optionally may be configured to determine whether one ormore electrodes 18 are in sufficient proximity to the area of tissue andto selectively apply the energy delivery patterns to those electrodesdetermined to be sufficiently proximate the area of tissue.

The electrodes 18 in the plurality of electrodes 18 may be uniformly orsymmetrically spaced apart from each other and radially arranged aboutthe elongate body longitudinal axis 28 and around a circumference of theexpandable element 30. Alternatively, the electrodes 18 may beun-uniformly or asymmetrically spaced apart. Uniformly spaced electrodes18 may allow for the even distribution of electric field strength duringpulsed high voltage energy deliveries and unevenly spaced electrodes 18may allow for a variable distribution of electric field strength.Although the term “plurality” is used to refer to different groups ofelectrodes of the plurality of electrodes 18, it will be understood thata single electrode 18 may have the characteristics described for aparticular group of electrodes. That is, for simplicity, a singleelectrode may be referred to as a “plurality of electrodes” for purposesof comparison to a different plurality of electrodes. Thus, a pluralityof electrodes 18 as referred to herein may include at least oneelectrode. For example, an expandable element 30 including a pluralityof electrodes 18, may include a first at least one electrode 18A and asecond at least one electrode 18B. Further, the electrodes 18 may bespaced and/or distributed of splines 41 of the expandable element 30 asdiscussed herein, in those embodiments in which the expandable element30 includes splines 41. That is, even though the figures show anexpandable element 30 that is inflatable, it will be understood that theexpandable element 30 may include one or more splines 41 in addition toor instead of the inflatable expandable element.

Referring now to FIGS. 5-10, the medical device 12 may have a firstelectrode configuration of electrodes that includes a plurality ofteardrop-shaped electrodes 18 on the expandable element 30. Optionally,the medical device 12 may also include a distal electrode 18″ at thedistalmost location on the expandable element 30. Each teardrop-shapedelectrode 18 may be tapered in a proximal-to-distal direction, with afirst or distal end 54 that is pointed and a second or proximal end 56that is rounded. This teardrop electrode shape may preserve consistentand uniform spacing between electrodes 18 when the expandable element 30is inflated. In one embodiment, the plurality of teardrop-shapedelectrodes 18 may be disposed over the distal portion 34 of theexpandable element 30, with the wider proximal ends 56 of the electrodes18 being at or proximate the equator 58 (for example, the widestcircumference lying in a plane that is orthogonal to, or at leastsubstantially orthogonal to, the elongate body longitudinal axis 28) ofthe inflated expandable element 30. Additionally, the electrodes 18 maybe radially arranged about the elongate body longitudinal axis 28. Inthis configuration, at least a portion of each electrodes 18 may beconfigured to be in contact with, for example, a circumference of tissuesurrounding a pulmonary vein when the expandable element 30 ispositioned in contact with a pulmonary vein ostium, and at least aportion of at least some of the plurality of electrodes 18 may beconfigured to be in contact with a tissue wall (such as a wall of achamber of a heart) when a lateral surface of the expandable element 30is positioned to be in contact with the tissue wall. However, it will beunderstood that the electrodes 18 shown in FIGS. 5-10 may be of anysuitable size, shape, and/or configuration and may be used to deliverenergy delivery patterns other than those explicitly shown. Further,although sixteen electrodes 18 are shown in FIGS. 5-10, it will beunderstood that more or fewer electrodes may be used.

In a first exemplary energy delivery pattern as shown in FIGS. 5 and 6,all of the plurality of electrodes 18 may be active or coupled to one ofthe polarities of the generator 14. Active electrodes are referred towith reference number 18A, and these electrodes 18A are also shaded inthe figures, and inactive electrodes (electrodes that are uncoupled fromboth polarities of the generator 14) are referred to with referencenumber 18B in FIGS. 5-21. Inactivating certain electrodes 18B in theseenergy delivery patterns may not only allow electroporation energy to bedelivered in a desired pattern, but may also affect the current densityat one or more locations, prevent loss of current into the blood and/orthe formation of coagulum, prevent overheating of certain electrodes,and/or affect the depth of electrical field penetration into tissue.Further, every other electrode 18A may be connected to a first (forexample, positive) polarity of the generator 14, and the interveningelectrodes 18A may be connected to a second (for example, negative)polarity of the generator 14. The electrodes 18 are each furtheridentified with the numbers E1-E16, representing the sixteen electrodesshown in FIGS. 5-10. The symbol “+” is used to depict electrodes incommunication with the positive polarity and the symbol “−” is used todepict electrodes in communication with the negative polarity. However,it will be understood that opposite polarities of those shown in FIGS.5-21 may be used for each electrode. In the energy delivery patternshown in FIGS. 5 and 6, all electrodes 18A may be active, withelectrodes E1, E3, E5, E7, E9, E11, E13, and E15 being connected to thenegative polarity of the generator 14 and electrodes E2, E4, E6, E8,E10, E12, E14, and E16 being connected to the positive polarity of thegenerator 14. In this configuration, bipolar energy may be deliveredbetween adjacent pairs of active electrodes 18A with oppositepolarities, such as between electrodes E1 and E2, between electrodes E2and E3, between electrodes E3 and E4, and so on. As adjacent electrodes18A may be active, this configuration may be useful for recordingmapping signals because of the reduced spacing between active electrodepairs. Additionally or alternatively, the electrodes 18A may be used todeliver electroporation energy.

In a second exemplary energy delivery pattern as shown in FIGS. 7 and 8,fewer than all of the electrodes 18 may be active (that is, a firstplurality of electrodes 18A may be active), with the remainingelectrodes (that is, a second plurality of electrodes 18B) beinginactive or uncoupled from the generator 14. Inactive electrodes arereferred to with reference number 18B in FIGS. 5-21. In the energydelivery pattern shown in FIGS. 7 and 8, every other electrode 18A maybe active and connected to the generator 14 (electrodes E1, E3, ES, E7,E9, E11, E13, and E15). Of these, every other active electrode 18A maybe connected to the negative polarity of the generator 14 (electrodesE1, E5, E9, and E13) and the intervening active electrodes may beconnected to the positive polarity of the generator 14 (electrodes E3,E7, E11, and E15). The inactive electrodes 18B may be electrodes E2, E4,E6, E8, E10, E12, E14, and E16. In this configuration, bipolar energymay be delivered between adjacent pairs of active electrodes 18A withopposite polarities, such as between electrodes E1 and E3, betweenelectrodes E3 and E5, between electrodes E5 and E7, and so on. Theincreased distance between active electrode pairs may help drive theelectroporation energy deeper into the target tissue than the energydelivery pattern shown in FIGS. 5 and 6.

In a third exemplary energy delivery pattern as shown in FIGS. 9 and 10,fewer than all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The groupsof active 18A and inactive 18B electrodes may be the opposite of thosegroups shown in FIGS. 7 and 8. In the energy delivery pattern shown inFIGS. 9 and 10, every other electrode 18A may be active and connected tothe generator 14 (electrodes E2, E4, E6, E8, E10, E12, E14, and E16). Ofthese, every other active electrode 18A may be connected to the negativepolarity of the generator 14 (electrodes E2, D6, E10, and E14) and theintervening active electrodes may be connected to the positive polarityof the generator 14 (electrodes E4, E8, E12, and D16). The inactiveelectrodes 18B may be electrodes E1, E3, E5, E7, E9, E11, E13, and E15.In this configuration, bipolar energy may be delivered between adjacentpairs of active electrodes 18A with opposite polarities, such as betweenelectrodes E2 and E4, between electrodes E4 and E6, between electrodesE6 and E8, and so on.

Referring now to FIGS. 11-21, the medical device 12 may have a secondelectrode configuration of electrodes that includes a plurality of roundelectrodes 18 on the expandable element 30. As a non-limiting example,the plurality of electrodes 18 may be disposed over the distal portion34 of the expandable element and may be radially arranged about theelongate body longitudinal axis 28. Although the electrodes may bedisposed around an entirety of a circumference of the expandable element30, twenty-four electrodes are shown in the side views of FIGS. 11-21and will be specifically discussed herein for simplicity. Additionally,the electrodes shown in FIGS. 11-21 will be referred to as being in oneof four series S1-S4, with each series extending around an entirety of acircumference of the expandable element 30. It will be understood thatmore or fewer electrodes than those shown may be used, and that otherelectrode sizes, shapes, and/or configurations may be used. As in FIGS.5-10, the active electrodes 18A are shaded in FIGS. 11-21. Inactiveelectrodes 18B are not shaded.

In a first exemplary energy delivery pattern as shown in FIG. 11, fewerthan all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be at least some of those electrodes in series S1.For example, every other electrode 18A may be active and connected tothe generator 14 (electrodes E1, E3, E5, for example). Of these, everyother active electrode 18A may be connected to the negative polarity ofthe generator 14 (electrode E3, for example) and the intervening activeelectrodes 18A may be connected to the positive polarity of thegenerator 14 (electrodes E1 and E5, for example). The inactiveelectrodes 18B may be, for example, electrodes E2, E4, and E6 of seriesS1 and all electrodes of all of series S2-S4 (E7-E24, for example). Inthis configuration, bipolar energy may be delivered between adjacentpairs of active electrodes 18A in series S1 with opposite polaritiesthat are located around the circumference of the expandable element 30.

In a second exemplary energy delivery pattern as shown in FIG. 12, fewerthan all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be at least some of those electrodes in series S1 andS3. For example, every other electrode 18A may be active and connectedto the generator 14 (electrodes E1, E3, E5, E15, E17, and E19, forexample). Of these, every other active electrode 18A may be connected tothe negative polarity of the generator 14 (electrodes E3 and E17, forexample) and the intervening active electrodes 18A may be connected tothe positive polarity of the generator 14 (electrodes E1, E5, E15, andE19, for example). The inactive electrodes 18B may be, for example,electrodes E2, E4, and E6 of series S1, electrodes E14, E16, and E18 ofseries S3, and all electrodes of all of series S2 and S4 (E7-E13 andE20-E24, for example). In this configuration, bipolar energy may bedelivered between adjacent pairs of active electrodes 18A in series S1with opposite polarities, between adjacent pairs of active electrodes18A in series S3 with opposite polarities, and between electrodes withopposite polarities between series S1 and S3.

In a third exemplary energy delivery pattern as shown in FIG. 13, fewerthat all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be all electrodes in series S2 (electrodes E7-E13,for example) and all electrodes in series S4 (electrodes E20-E24, forexample). All electrodes 18A in series S2 may be connected to thepositive polarity of the generator 14 and all electrodes 18A in seriesS4 may be connected to the negative polarity of the generator 14. Allelectrodes 18B in series S1 and S3 may be inactive.

In a fourth exemplary energy delivery pattern as shown in FIG. 14, fewerthan all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be every other electrode in series S1 (electrodes E1,E3, and E5, for example), every other electrode in series S2 (electrodesE8, E10, and E12, for example), every other electrode in series S3(electrodes E15, E17, and E19, for example), and every other electrodein series S4 (electrodes E21 and E23, for example). Of these activeelectrodes 18A, every other electrode 18A may be connected to thenegative polarity of the generator 14 and the intervening activeelectrodes 18A may be connected to the positive polarity of thegenerator 14. The remaining electrodes in series S1-S4 may be inactive.

In a fifth exemplary energy delivery pattern as shown in FIG. 15, all ofthe electrodes 18 may be active. Every other active electrode 18A ofeach of series S1-S4 may be connected to the negative polarity of thegenerator 14 and the intervening active electrodes 18A may be connectedto the positive polarity of the generator 14 (electrodes E1, E5, E15,and E19, for example). The inactive electrodes 18B may be, for example,electrodes E2, E4, and E6 of series S1, electrodes E14, E16, and E18 ofseries S3, and all electrodes of all of series S2 and S4 (E7-E13 andE20-E24, for example). In this configuration, bipolar energy may bedelivered between adjacent pairs of active electrodes 18A in series S1with opposite polarities, between adjacent pairs of active electrodes18A in series S3 with opposite polarities, and between electrodes withopposite polarities between series S1 and S3.

In a sixth exemplary energy delivery pattern as shown in FIG. 16, all ofthe electrodes 18 may be active. Every electrode 18A of each of seriesS2 and S4 may be connected to the negative polarity of the generator 14and every electrode 18A of each of series S1 and S3 may be connected tothe positive polarity of the generator 14 (electrodes E1, E5, E15, andE19, for example).

In a seventh exemplary energy delivery pattern as shown in FIG. 17,fewer than all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may all electrodes in series S1 and S3, with theelectrodes 18A in series S1 being connected to the positive polarity ofthe generator 14 and the electrodes 18A in series S3 being connected tothe negative polarity of the generator 14. The remaining electrodes inseries S2 and S4 may be inactive.

In an eighth exemplary energy delivery pattern as shown in FIG. 18,fewer than all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may all electrodes in series S1 and S2, with theelectrodes 18A in series S1 being connected to the positive polarity ofthe generator 14 and the electrodes 18A in series S2 being connected tothe negative polarity of the generator 14. The remaining electrodes inseries S3 and S4 may be inactive.

In a ninth exemplary energy delivery pattern as shown in FIG. 19, fewerthan all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be all electrodes in series S1. Of these, every otheractive electrode 18A may be connected to the negative polarity of thegenerator 14 and the intervening active electrodes 18A may be connectedto the positive polarity of the generator 14. The inactive electrodes18B may be all electrodes of series S2-S4.

In a tenth exemplary energy delivery pattern as shown in FIG. 20, fewerthan all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be all electrodes in series S1 and S2. Of these,every other active electrode 18A may be connected to the negativepolarity of the generator 14 and the intervening active electrodes 18Amay be connected to the positive polarity of the generator 14. Theinactive electrodes 18B may be all electrodes of series S3 and S4.

In an eleventh exemplary energy delivery pattern as shown in FIG. 21,fewer than all of the electrodes 18 may be active, with the remainingelectrodes being inactive or uncoupled from the generator 14. The activeelectrodes 18A may be all electrodes in series S1 and S4. All electrodes18A in series Si may be connected to the positive polarity of thegenerator 14 and all electrodes 18A in series S4 may be connected to thenegative polarity of the generator 14. The inactive electrodes 18B maybe all electrodes of series S2 and S3.

As a non-limiting example, after a train of biphasic pulses has beendelivered in a first delivery pattern (for example, as shown in FIG.11), the processing circuitry 50 and/or CEDS 16 may then switchelectrode connection(s) to the generator 14 such that energy isdelivered in a second energy delivery pattern (for example, as shown inFIG. 12). After a train of biphasic pulses has been delivered in thesecond delivery pattern, the processing circuitry 50 and/or CEDS 16 maythen switch electrode connection(s) to the generator 14 such that energyis delivered in a third delivery pattern (for example, as shown in FIG.13), and so on. The use of multiple delivery patterns at the samepositioning of the expandable element 30 on the tissue surface may causethe underlying tissue to experience multiple electric field vectordirections, thereby causing a larger percentage of cells exposed toelectroporation and effectively electroporated. The delivery of energyin a sequence of multiple energy delivery patterns may be automatedcontrolled by the processing circuitry 50 and may be accomplished byswitching which electrodes 18 are connected to each polarity from thegenerator 14 with high-voltage vacuum relays or the like.

The medical device 10 may energize specific electrodes 18 with selectedpolarities or may combine groups of electrodes for pulsed electric fielddelivery. Using the various energy delivery patterns as shown in FIGS.5-21, a fully circumferential lesion may be created when the electrodes18 are activated or a localized lesion that is not circumferential canbe created. Contiguous transmural lesions, which may be located deepwithin or at the surface of target tissue, may be created with these, orother, energy delivery patterns. These are non-limiting examples ofdifferent energy delivery patterns that may be used so that veryspecific areas of tissue can be ablated. As a non-limiting example, theenergy delivery patterns may be delivered to tissue in quick succession.Alternatively, a single energy delivery pattern or series of energydelivery patterns may be repeatedly delivered to target tissue.

In one embodiment, a medical system 10 includes a medical device 12configured to electroporate tissue, the medical device 12 including anexpandable element 30, the expandable element 30 having a plurality ofelectrodes 18; and an energy generator 14 in communication with theplurality of electrodes 18, the energy generator 14 having processingcircuitry 50 configured to: deliver electroporation energy to theplurality of electrodes 18; receive data from the plurality ofelectrodes 18; determine whether an alert condition is present based onthe data received from the plurality of electrodes 18; and at least oneof cease a delivery of electroporation energy to the plurality ofelectrodes 18 and prevent the delivery of electroporation energy to theplurality of electrodes 18 when the processing circuitry 50 determinesthe alert condition is present.

In one aspect of the embodiment, the data includes impedancemeasurements.

In one aspect of the embodiment, the plurality of electrodes isconfigured to be uniformly spaced when the expandable element 30 isexpanded.

In one aspect of the embodiment, each of the plurality of electrodes 18is configured to record at least one impedance measurement, theprocessing circuitry 50 being configured to receive the at least oneimpedance measurement from each of the plurality of electrodes 18 andselectively activate at least one of the plurality of electrodes 18based on the at least one impedance measurement received from each ofthe plurality of electrodes 18.

In one aspect of the embodiment, the system 10 further includes amapping system 48, and the energy generator and processing circuitry arefurther configured to selectively connect each of the plurality ofelectrodes to the mapping system 48 and record intracardiac electrogramsignals from each of the plurality of electrodes 18.

In one aspect of the embodiment, the expandable element 30 has a distalportion 34 and a proximal portion 32, the plurality of electrodes 18being disposed on the distal portion 34 of the expandable element 30.

In one aspect of the embodiment, the medical device 12 may furtherinclude at least one electrode 18 distal to the expandable element 30.

In one aspect of the embodiment, the at least one electrode 18 distal tothe expandable element 30 is on a secondary medical device 38 that ispositionable distal to the medical device 12.

In one aspect of the embodiment, the medical device 12 further includesa distal tip 39 that extends distally beyond the expandable element 30,the at least one electrode 18 distal to the expandable element 30 beingon the distal tip 39.

In one aspect of the embodiment, the energy generator 14 is configuredto deliver electroporation energy to the plurality of electrodes 18 in asequence of a plurality of energy delivery patterns.

In one aspect of the embodiment, the processing circuitry 50 isconfigured to automatically switch between the plurality of energydelivery patterns such that a pulse train of electroporation energy isdelivered in each of the plurality of energy delivery patterns at leastonce when the system 10 is in use.

In one aspect of the embodiment, the medical device 12 further includesa longitudinal axis 28, each of the plurality of electrodes 18 having ateardrop shape that is tapered in a proximal-to-distal direction, theplurality of electrodes 18 being radially arranged around thelongitudinal axis 28.

In one embodiment, a medical system 10 includes a medical device 12configured to electroporate an area of tissue, the medical device 12including: a balloon 30 having a distal portion 34 and a proximalportion 32; and a plurality of electrodes 18 disposed on the distalportion 34 of the balloon 30, each of the plurality of electrodes 18being configured to record impedance signals from the area of tissue anddeliver electroporation energy to the area of tissue; and an energygenerator 14 in communication with the plurality of electrodes 18, theenergy generator 14 having processing circuitry 50 configured to:receive impedance signals from the plurality of electrodes 18; identifyat least one electrode 18 of the plurality of electrodes 18 that is incontact with the area of tissue based on impedance signals received fromthe plurality of electrodes 18; determine whether the plurality ofelectrodes 18 has uniform spacing when the balloon 30 is inflated basedon impedance signals received from the plurality of electrodes 18; allowa delivery of electroporation energy to the plurality of electrodes 18when the processing circuitry 50 determines the plurality of electrodes18 has uniform spacing when the balloon 30 is inflated; and selectivelydeliver electroporation energy to the at least one electrode 18 of theplurality of electrodes 18 that the processing circuitry identifies asbeing in contact with the area of tissue.

In one aspect of the embodiment, the medical device 12 further includesa longitudinal axis 28, each of the plurality of electrodes 18 having ateardrop shape that is tapered in a proximal-to-distal direction, theplurality of electrodes 18 being radially arranged around thelongitudinal axis 28.

In one aspect of the embodiment, the balloon 30 has a circumference,each of the plurality of electrodes 18 having a circular shape and theplurality of electrodes 18 being radially arranged around thecircumference of the balloon 30.

In one aspect of the embodiment, the energy generator 14 is configuredto deliver electroporation energy to the plurality of electrodes 18 in aplurality of energy delivery patterns.

In one aspect of the embodiment, the energy generator 14 is configuredto deliver bipolar electroporation energy between adjacent pairs of theplurality of electrodes 18 to the area of tissue, the plurality ofenergy delivery patterns being a sequence of at least five energydelivery patterns.

In one aspect of the embodiment, the energy generator 14 is configuredto deliver monopolar electroporation energy between at least one of theplurality of electrodes 18 and a supplemental electrode 18 locateddistal to the balloon 30.

In one embodiment, a method for electroporating tissue includes:positioning an expandable element 30 of a medical device 12 proximate anarea of target tissue, the expandable element 30 including a pluralityof electrodes 18, each of the plurality of electrodes 18 beingconfigured to record impedance measurements; recording impedancemeasurements with each of the plurality of electrodes 18; transmittingthe recorded impedance measurement to an energy generator 14;identifying, based on the recorded impedance measurements, at least oneelectrode 18 of the plurality of electrodes 18 that is in contact withthe area of target tissue and that is a predetermined distance from atleast one adjacent electrode 18 of the plurality of electrodes 18; andthen delivering electroporation energy to the identified at least oneelectrode 18 in a sequence of energy delivery patterns by selectivelyone of activating and deactivating each of the at least one electrode 18of the plurality of electrodes 18.

In one aspect of the embodiment, the method further includes deliveringthe sequence of energy delivery patterns such that there is a delayfollowing each energy delivery pattern in the sequence of energydelivery patterns and each energy delivery pattern in the sequence ofenergy delivery patterns has a duration that is at least as long as acorresponding following delay.

In one embodiment, a medical system 10 includes: a medical device 12configured to electroporate a targeted area of tissue, the medicaldevice 12 including: an expandable element 30 having a plurality ofsplines 41, each of the plurality of splines 41 having a distal portion41A and a proximal portion 41B, the plurality of splines 41 beingtransitionable between a linear first configuration and an expandedsecond configuration; and a plurality of electrodes 18 disposed on thedistal portions 41A of the plurality of splines 41, each of theplurality of electrodes 18 being configured to record impedance signalsfrom the targeted area of tissue and deliver electroporation energy tothe targeted area of tissue; and an energy generator 14 in communicationwith the plurality of electrodes 18, the energy generator 14 havingprocessing circuitry 50 configured to: deliver electroporation energy tothe plurality of electrodes 18 in a sequence of a plurality of energydelivery patterns; and automatically switch between the plurality ofenergy delivery patterns of the sequence of the plurality of energydelivery patterns such that a pulse train of electroporation energy isdelivered in each of the plurality of energy delivery patterns at leastonce when the system is in use.

In one aspect of the embodiment, the processing circuitry 50 is furtherconfigured to: receive impedance signals from the plurality ofelectrodes 18; identify at least one electrode 18 of the plurality ofelectrodes 18 that is located proximate the targeted area of tissuebased on the impedance signals received from the plurality of electrodes18; and selectively deliver electroporation energy to the at least oneelectrode 18 of the plurality of electrodes 18 that the processingcircuitry 50 identifies as being located proximate the targeted area oftissue.

In one aspect of the embodiment, the processing circuitry 50 is furtherconfigured to: determine whether the plurality of electrodes 18 hasuniform spacing when the plurality of splines 41 are in the expandedsecond configuration based on impedance signals received from theplurality of electrodes 18; and allow a delivery of electroporationenergy to the plurality of electrodes 18 when the processing circuitry50 determines the plurality of electrodes 18 has uniform spacing whenthe plurality of splines 41 are in the expanded second configuration.

As will be appreciated by one of skill in the art, certain conceptsdescribed herein may be embodied as a method, data processing system,and/or computer program product. Accordingly, these concepts describedherein may take the form of an entirely hardware embodiment, an entirelysoftware embodiment or an embodiment combining software and hardwareaspects. Furthermore, the disclosure may take the form of a computerprogram product on a tangible computer usable storage medium havingcomputer program code embodied in the medium that can be executed by acomputer. Any suitable tangible computer readable medium may be utilizedincluding hard disks, CD-ROMs, electronic storage devices, opticalstorage devices, or magnetic storage devices.

It will be appreciated by persons skilled in the art that the presentinvention is not limited to what has been particularly shown anddescribed herein above. In addition, unless mention was made above tothe contrary, it should be noted that all of the accompanying drawingsare not to scale. A variety of modifications and variations are possiblein light of the above teachings without departing from the scope andspirit of the invention, which is limited only by the following claims.

What is claimed is:
 1. A medical device, comprising: an elongate bodyhaving a proximal end and a distal end; a lumen slidably disposed withinthe elongate body, the lumen having a distal opening; at least onespline slidably disposed within the elongate body and extending distallyfrom the distal end of the elongate body, the at least one spline havinga distal portion and a proximal portion opposite the distal portion; atleast one electrode disposed on the distal portion of the at least onespline; and a secondary medical device being slidably disposed withinthe lumen and extending from the distal opening of the lumen.
 2. Themedical device of claim 1, further including an expandable element, theat least one spline surrounding the expandable element.
 3. The medicaldevice of claim 2, wherein the expandable element is a balloon.
 4. Themedical device of claim 3, wherein at least a portion of the the distalportion of the at least one spline is insulated.
 5. The medical deviceof claim 1, wherein the at least one spline has a distal tip, the distaltip of the at least one spline being coupled with the distal opening ofthe lumen.
 6. The medical device of claim 5, wherein the lumen islongitudinally movable from a first position to a second position,movement of the lumen from the first position to the second positionmoves the at least one spline from a first linear configuration to asecond expanded configuration.
 7. The medical device of claim 6, whereinadvancement of the lumen within the elongate body extends the at leastone spline and retraction of the lumen within the elongate body retractsthe at least one spline.
 8. The medical device of claim 1, wherein eachof the at least one electrode includes at least one sensor.
 9. Themedical device of claim 1, wherein the one or more spline is a pluralityof splines.
 10. The medical device of claim 1, wherein the one or moreelectrodes is a plurality of electrodes.
 11. The medical device of claim1, wherein the secondary medical device has at least one electrode thatis sized to be received within the lumen.
 12. A medical device,comprising: an elongate body having a proximal end and a distal end; alumen slidably disposed within the elongate body, the lumen having adistal opening; a plurality of splines slidably disposed within theelongate body and extending distally from the distal end of the elongatebody, the plurality of splines having a distal portion with a distal tipand a proximal portion opposite the distal portion, the distal tip ofthe plurality of splines being coupled with the distal opening of thelumen; a plurality of electrodes disposed on the distal portion of theplurality of splines; an expandable element, the plurality of splinessurrounding the expandable element; and a secondary medical device beingslidably disposed within the lumen and extending from the distal openingof the lumen.
 13. The medical device of claim 12, wherein at least aportion of the distal portion of the plurality of splines is insulated.14. The medical device of claim 12, wherein the expandable element is aballoon.
 15. The medical device of claim 12, wherein the lumen islongitudinally movable from a first position to a second position,movement of the lumen from the first position to the second positionmoves the plurality of splines from a first linear configuration to asecond expanded configuration.
 16. The medical device of claim 15,wherein advancement of the lumen within the elongate body extends theplurality of splines and retraction of the lumen within the elongatebody retracts the plurality of splines.
 17. The medical device of claim12, wherein the plurality of electrodes includes at least one sensor.18. The medical device of claim 12, wherein the secondary medical devicehas at least one electrode that is sized to be received within thelumen.
 19. The medical device of claim 18, wherein the secondary medicaldevice is a guidewire and at least a portion of the guidewire is sizedto be received within the lumen.
 20. A medical system, comprising: amedical device comprising: an elongate body having a proximal end and adistal end; a lumen slidably disposed within the elongate body, thelumen having a distal opening; a plurality of spline slidably disposedwithin the elongate body and extending distally from the distal end ofthe elongate body, the plurality of splines having a distal portion witha distal tip and a proximal portion opposite the distal portion, thedistal tip of the plurality of splines being coupled with the distalopening of the lumen; a plurality of electrodes disposed on the distalportion of the plurality of splines; an expandable element, theplurality of splines surrounding the expandable element; a secondarymedical device being slidably disposed within the lumen and extendingfrom the distal opening of the lumen an energy generator incommunication with the plurality of electrodes, the energy generatorhaving processing circuitry configured to: deliver electroporationenergy to the plurality of electrodes; receive data from the pluralityof electrodes; determine whether an alert condition is present based onthe data received from the plurality of electrodes; and at least one ofcease a delivery of electroporation energy to the plurality ofelectrodes and prevent the delivery of electroporation energy to theplurality of electrodes when the processing circuitry determines thealert condition is present.